{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:15:56Z","timestamp":1785413756036,"version":"3.56.0"},"reference-count":127,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009057","name":"University of Graz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009057","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01faaaf77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The gut microbiome has emerged as a critical determinant of health and disease across virtually all organ systems. In the context of chronic kidney disease (CKD) and renal transplantation, mounting evidence reveals a complex bidirectional relationship between the intestinal microbiota and kidney function\u2014commonly referred to as the gut\u2013kidney axis. Patients with CKD harbor a profoundly altered gut microbial ecosystem characterized by reduced diversity, depletion of beneficial commensal organisms, and expansion of pathobiont taxa capable of generating uremic toxins and pro-inflammatory mediators. These perturbations are further compounded by the uremic milieu itself, dietary restrictions, frequent antibiotic exposure, and the use of immunosuppressive agents following transplantation. The gut\u2013liver\u2013kidney axis adds an additional layer of complexity, linking hepatic metabolism, bile acid signaling, endotoxemia, and systemic immune activation to the progression of renal disease. Gut-derived metabolites\u2014including short-chain fatty acids (SCFAs), bile acids, trimethylamine N-oxide (TMAO), and tryptophan-derived uremic solutes such as indoxyl sulfate and p-cresyl sulfate\u2014serve as molecular mediators of inter-organ crosstalk and have been identified as both biomarkers and therapeutic targets. A growing body of literature supports the diagnostic and prognostic utility of microbiome composition and its metabolic signatures in patients with CKD and those undergoing renal replacement therapy. Therapeutic strategies aimed at restoring microbial homeostasis\u2014encompassing dietary interventions, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), bile acid\u2013based therapies, and novel pharmacological approaches\u2014hold considerable promise for improving outcomes in CKD and transplant recipients. Importantly, the bidirectional relationship between immunosuppressive drugs and the gut microbiota has emerged as a clinically significant determinant of both microbial ecology and drug pharmacokinetics: each major immunosuppressive agent class\u2014corticosteroids, calcineurin inhibitors, mycophenolate mofetil, and mTOR inhibitors\u2014induces characteristic dysbiotic patterns, while in turn, the microbiota modulates drug bioavailability through enzymatic biotransformation (notably bacterial beta-glucuronidase activity affecting mycophenolic acid enterohepatic recirculation) and modulation of host drug-metabolizing enzymes. This narrative review provides a comprehensive overview of the current understanding of microbiome dysbiosis in the setting of renal disease and transplantation, examines the mechanistic underpinnings of the gut\u2013liver\u2013kidney axis, details the multifaceted impact of dysbiosis on transplant outcomes\u2014including allograft function and rejection, infection, post-transplant diabetes, and cardiovascular complications\u2014and critically appraises the translational potential of microbiome-targeted interventions. We conclude by highlighting ongoing challenges and future directions toward personalized, microbiome-informed clinical care.<\/jats:p>","DOI":"10.3390\/jcm15145648","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"5648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-Targeted Modulation in Renal Transplantation"],"prefix":"10.3390","volume":"15","author":[{"given":"Hans Michael","family":"Hau","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Jahn","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Karitnig","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro Michael","family":"Hasenh\u00fctl","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sucher","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Stiegler","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Laudi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e669","DOI":"10.1002\/mco2.669","article-title":"Posttransplant complications: Molecular mechanisms and therapeutic interventions","volume":"5","author":"Liu","year":"2024","journal-title":"MedComm"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJMra1802677","article-title":"Antibody-Mediated Rejection of Solid-Organ Allografts","volume":"379","author":"Loupy","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","first-page":"8","article-title":"Common complications post-kidney transplantation: A literature review","volume":"2021","author":"Alharthi","year":"2021","journal-title":"Int. J. Community Med. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhu, N., Su, X., Gao, Y., and Yang, R. (2023). Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells, 12.","DOI":"10.3390\/cells12050793"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4735040","DOI":"10.1155\/2019\/4735040","article-title":"Gut Microbiota Modulation on Intestinal Mucosal Adaptive Immunity","volume":"2019","author":"Wang","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The Human Intestinal Microbiome in Health and Disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kho, Z.Y., and Lal, S.K. (2018). The Human Gut Microbiome\u2014A Potential Controller of Wellness and Disease. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01835"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s41581-019-0172-1","article-title":"Intestinal microbiome and fitness in kidney disease","volume":"15","author":"Meijers","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1007\/s00467-016-3527-x","article-title":"The gut-kidney axis","volume":"32","author":"Evenepoel","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bhargava, S., Merckelbach, E., Noels, H., Vohra, A., and Jankowski, J. (2022). Homeostasis in the Gut Microbiota in Chronic Kidney Disease. Toxins, 14.","DOI":"10.3390\/toxins14100648"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rysz, J., Franczyk, B., \u0141awi\u0144ski, J., Olszewski, R., Cia\u0142kowska-Rysz, A., and Gluba-Brz\u00f3zka, A. (2021). The Impact of CKD on Uremic Toxins and Gut Microbiota. Toxins, 13.","DOI":"10.3390\/toxins13040252"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic kidney disease alters intestinal microbial flora","volume":"83","author":"Vaziri","year":"2012","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12964-025-02625-x","article-title":"Targeting gut\u2013liver\u2013kidney axis: Microbiota-derived metabolites and therapeutic implications","volume":"24","author":"Zhang","year":"2026","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","article-title":"The gut-liver axis and the intersection with the microbiome","volume":"15","author":"Tripathi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Swarte, J., Douwes, R., Hu, S., Vich Vila, A., Eisenga, M.F., van Londen, M., Gomes-Neto, A.W., Weersma, R.K., Harmsen, H.J.M., and Bakker, S.J.L. (2020). Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020386"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/scitranslmed.abn7566","article-title":"Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation","volume":"14","author":"Swarte","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12967-025-07465-4","article-title":"Longitudinal profiling of gut microbiota dynamics in kidney transplant recipients","volume":"24","author":"Zhong","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lee, J.R., Muthukumar, T., Dadhania, D., Taur, Y., Jenq, R.R., Toussaint, N.C., Ling, L., Pamer, E., and Suthanthiran, M. (2015). Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122399"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"sfae214","DOI":"10.1093\/ckj\/sfae214","article-title":"Kidney transplantation and gut microbiota","volume":"17","author":"Chen","year":"2024","journal-title":"Clin. Kidney J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"44709","DOI":"10.1038\/s41598-025-28725-9","article-title":"Gut microbiome and metabolite signatures for predicting acute kidney transplant rejection: A prospective study","volume":"15","author":"Cho","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.ajt.2025.02.010","article-title":"Gut microbiome alterations precede graft rejection in kidney transplantation patients","volume":"25","author":"Holle","year":"2024","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Campbell, P.M., Humphreys, G.J., Summers, A.M., Konkel, J.E., Knight, C.G., Augustine, T., and McBain, A.J. (2020). Does the Microbiome Affect the Outcome of Renal Transplantation?. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.558644"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alobaidi, S. (2025). The gut\u2013kidney axis in chronic kidney disease: Mechanisms, microbial metabolites, and microbiome-targeted therapeutics. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1675458"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, C., Wang, J., Lei, L., Li, L., and Yuan, X. (2025). Gut microbiota therapy for chronic kidney disease. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1660226"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1186\/s40001-026-04100-w","article-title":"Gut dysbiosis in kidney injury: Therapeutic potential of fecal microbiota transplantation","volume":"31","author":"Liu","year":"2026","journal-title":"Eur. J. Med. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, Q., Han, Y., Pang, L., Zhou, Z., and Dai, L. (2025). Gut microbiome remodeling in chronic kidney disease: Implications of kidney replacement therapies and therapeutic interventions. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1620247"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, X., Liu, X., Gong, F., Jiang, Y., Zhang, C., Zhou, W., and Zhang, W. (2025). Targeting gut microbiota for diabetic nephropathy treatment: Probiotics, dietary interventions, and fecal microbiota transplantation. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1621968"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1159\/000444066","article-title":"Physiological Role of Gut Microbiota for Maintaining Human Health","volume":"93","author":"Andoh","year":"2016","journal-title":"Digestion"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.jcmgh.2021.02.007","article-title":"Regulation of Intestinal Barrier Function by Microbial Metabolites","volume":"11","author":"Ghosh","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jare.2025.05.015","article-title":"The functions of gut microbiota-mediated bile acid metabolism in intestinal immunity","volume":"80","author":"He","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00394-017-1445-8","article-title":"Gut microbiota functions: Metabolism of nutrients and other food components","volume":"57","author":"Rowland","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zeng, L., Qian, Y., Cui, X., Zhao, J., Ning, Z., Cha, J., Wang, K., Ge, C., Jia, J., and Dou, T. (2025). Immunomodulatory role of gut microbial metabolites: Mechanistic insights and therapeutic frontiers. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1675065"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e7502","DOI":"10.7717\/peerj.7502","article-title":"Factors affecting the composition of the gut microbiota, and its modulation","volume":"7","author":"Hasan","year":"2019","journal-title":"PeerJ"},{"key":"ref_36","first-page":"26050","article-title":"The composition of the gut microbiota throughout life, with an emphasis on early life","volume":"26","author":"Murphy","year":"2015","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature11053","article-title":"Human gut microbiome viewed across age and geography","volume":"486","author":"Yatsunenko","year":"2012","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/joim.20089","article-title":"Gut microbiota development across the lifespan: Disease links and health-promoting interventions","volume":"297","author":"Schoultz","year":"2025","journal-title":"J. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Aleman, F.D.D., and Valenzano, D. (2019). Microbiome evolution during host aging. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007727"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41575-018-0061-2","article-title":"You are what you eat: Diet, health and the gut microbiota","volume":"16","author":"Zmora","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.chom.2023.01.009","article-title":"Gut microbiome lipid metabolism and its impact on host physiology","volume":"31","author":"Brown","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.molcel.2020.03.005","article-title":"From Association to Causality: The Role of the Gut Microbiota and Its Functional Products on Host Metabolism","volume":"78","author":"Koh","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Campbell, C., Kandalgaonkar, M., Golonka, R., Yeoh, B., Vijay-Kumar, M., and Saha, P. (2023). Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020294"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.14336\/AD.2022.0104","article-title":"Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives","volume":"13","author":"Liu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism","volume":"24","author":"Sayin","year":"2016","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.copbio.2015.08.015","article-title":"Pathways and Functions of Gut Microbiota Metabolism Impacting Host Physiology","volume":"36","author":"Krishnan","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.chom.2024.04.004","article-title":"Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology","volume":"32","author":"Li","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ye, J., Yao, J., He, F., Sun, J., Zhao, Z., and Wang, Y. (2023). Regulation of gut microbiota: A novel pretreatment for complications in patients who have undergone kidney transplantation. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1169500"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Souai, N., Zidi, O., Mosbah, A., Kosai, I., El Manaa, J., Mokhtar, N.B., Asimakis, E., Stathopoulou, P., Cherif, A., and Tsiamis, G. (2020). Impact of the Post-Transplant Period and Lifestyle Diseases on Human Gut Microbiota in Kidney Graft Recipients. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111724"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/nep.13853","article-title":"Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients","volume":"26","author":"Chan","year":"2021","journal-title":"Nephrology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"105191","DOI":"10.1016\/j.micpath.2021.105191","article-title":"The Alteration human of gut microbiota and metabolites before and after renal transplantation","volume":"160","author":"Yu","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/MNH.0b013e328358c8d5","article-title":"CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity","volume":"21","author":"Vaziri","year":"2012","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000360010","article-title":"Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD","volume":"39","author":"Wong","year":"2014","journal-title":"Am. J. Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00678","DOI":"10.1002\/mbo3.678","article-title":"Altered gut microbiota and microbial biomarkers associated with chronic kidney disease","volume":"8","author":"Lun","year":"2018","journal-title":"Microbiologyopen"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1038\/s41598-017-02989-2","article-title":"Alteration of the gut microbiota in Chinese population with chronic kidney disease","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000345969","article-title":"Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in CKD","volume":"37","author":"Vaziri","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/ki.2012.440","article-title":"The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease","volume":"83","author":"Anders","year":"2013","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2215\/CJN.04610510","article-title":"Circulating endotoxemia: A novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease","volume":"6","author":"McIntyre","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/ki.2015.255","article-title":"Probiotics and chronic kidney disease","volume":"88","author":"Koppe","year":"2015","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"European Uremic Toxin Work Group (EUTox). Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000324885","article-title":"Indoxyl sulfate downregulates renal expression of Klotho through production of ROS and activation of nuclear factor-\u0138B","volume":"33","author":"Shimizu","year":"2011","journal-title":"Am. J. Nephrol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e002767","DOI":"10.1161\/JAHA.115.002767","article-title":"Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-\u03baB","volume":"5","author":"Seldin","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1053\/j.gastro.2014.10.042","article-title":"Gut-liver axis in alcoholic liver disease","volume":"148","author":"Szabo","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"774","DOI":"10.2215\/CJN.12451018","article-title":"Hepatorenal Syndrome","volume":"14","author":"Francoz","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1073\/pnas.1215927110","article-title":"Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation","volume":"110","author":"Pluznick","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/ki.2011.355","article-title":"High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease","volume":"81","author":"Krishnamurthy","year":"2011","journal-title":"Kidney Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.2337\/db06-1642","article-title":"Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy","volume":"56","author":"Jiang","year":"2007","journal-title":"Diabetes"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease","volume":"116","author":"Tang","year":"2014","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Lin, C.-J., Wu, V., Wu, P.-C., and Wu, C.-J. (2015). Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132589"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1053\/j.jrn.2010.05.002","article-title":"Indoxyl sulfate is a nephro-vascular toxin","volume":"20","author":"Niwa","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1136\/gutjnl-2019-319766","article-title":"Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Mart\u00ednez, Y., Borriello, M., Capolongo, G., Ingrosso, D., and Perna, A. (2023). The Gut Microbiota in Kidney Transplantation: A Target for Personalized Therapy?. Biology, 12.","DOI":"10.3390\/biology12020163"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Rusu, M., Ichim, C., Anderco, P., P\u0103l\u0103\u0219tea, A., and Boicean, A. (2026). Gut-Kidney Axis: Unraveling the Role of the Microbiome in Chronic Kidney Disease. Biomedicines, 14.","DOI":"10.3390\/biomedicines14010109"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/s41579-025-01271-x","article-title":"The gut microbiome in solid-organ and haematopoietic-stem-cell transplantation","volume":"24","author":"Swarte","year":"2026","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41581-025-00988-5","article-title":"Microbiota and kidney disease: The road ahead","volume":"21","author":"Bloom","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"90194","DOI":"10.5500\/wjt.v14.i1.90194","article-title":"Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation","volume":"14","author":"Salvadori","year":"2024","journal-title":"World J. Transplant."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5500\/wjt.v11.i3.16","article-title":"Microbiota, renal disease and renal transplantation","volume":"11","author":"Salvadori","year":"2021","journal-title":"World J. Transplant."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"153294","DOI":"10.1016\/j.bbrc.2026.153294","article-title":"Microbiota-targeted modulation of the gut-kidney axis in diabetic kidney disease: Therapeutic advances and future perspectives","volume":"800","author":"Zhang","year":"2026","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00281-024-01012-x","article-title":"Gut microbiota-derived metabolites tune host homeostasis fate","volume":"46","author":"Kim","year":"2024","journal-title":"Semin. Immunopathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S268","DOI":"10.4285\/ATW2022.F-4075","article-title":"A potential role of gut microbiome in predicting of early acute rejection after kidney transplantation","volume":"36","author":"Kim","year":"2022","journal-title":"Korean J. Transplant."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e14260","DOI":"10.1111\/ctr.14260","article-title":"Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea","volume":"35","author":"Zhang","year":"2021","journal-title":"Clin. Transplant."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12967-024-05964-4","article-title":"Advancements in noninvasive techniques for transplant rejection: From biomarker detection to molecular imaging","volume":"23","author":"Song","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1111\/tri.13696","article-title":"Enteric dysbiosis in liver and kidney transplant recipients: A systematic review","volume":"33","author":"Sivaraj","year":"2020","journal-title":"Transpl. Int."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Guo, H., Pan, L., Wu, Q., Wang, L., Huang, Z., Wang, J., Wang, L., Fang, X., Dong, S., and Zhu, Y. (2025). Type 2 Diabetes and the Multifaceted Gut-X Axes. Nutrients, 17, (In English).","DOI":"10.3390\/nu17162708"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13098-025-02037-4","article-title":"Gut microbiota: An important player in diabetic kidney disease","volume":"18","author":"Shi","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Jiang, H., Wang, X., Zhou, W., Huang, Z., and Zhang, W. (2025). Gut microbiota dysbiosis in diabetic nephropathy: Mechanisms and therapeutic targeting via the gut-kidney axis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1661037"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2517402","DOI":"10.1080\/0886022X.2025.2517402","article-title":"Gut microbiota implication in diabetic kidney disease: Mechanisms and novel therapeutic strategies","volume":"47","author":"Zhang","year":"2025","journal-title":"Ren. Fail."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1681\/ASN.0000000896","article-title":"Kidney Disease as a Driver of Immunosenescence: Mechanisms and Potential Interventions","volume":"37","author":"Song","year":"2026","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"gfae069-0990-2751","DOI":"10.1093\/ndt\/gfae069.990","article-title":"#2751 CD14++CD16+ monocytes and CD8+ T cells are independently associated with annual change in eGFR and proteinuria in kidney transplant recipients","volume":"39","author":"Duni","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_94","first-page":"1708","article-title":"MO977: Circulating CD14++CD16+MONocytes, NK Cells and LYMPHOcyte Subsets Correlate with Conventional and Novel Deformation Related Indices of Left Ventricular Function in Kidney Transplant Recipients with no Established Cardiovascular Disease","volume":"37","author":"Duni","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"A16605","DOI":"10.1161\/circ.138.suppl_1.16605","article-title":"Abstract 16605: Peripheral Blood-Derived Myeloid Subtypes Are Associated with Cardiac Allograft Vasculopathy","volume":"138","author":"Holzhauser","year":"2018","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"ra.24-00121","DOI":"10.3400\/avd.ra.24-00121","article-title":"Role of Gut Microbes in Hypertension: A Systematic Review of Literature","volume":"18","author":"Garde","year":"2025","journal-title":"Ann. Vasc. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e70168","DOI":"10.1002\/mco2.70168","article-title":"Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy","volume":"6","author":"Shen","year":"2025","journal-title":"MedComm"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1124\/dmd.118.084772","article-title":"Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites","volume":"47","author":"Guo","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/ajt.16836","article-title":"Immunosuppressive therapy after solid organ transplantation and the gut microbiota: Bidirectional interactions with clinical consequences","volume":"22","author":"Gabarre","year":"2022","journal-title":"Am. J. Transpl."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2215\/CJN.05240515","article-title":"Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial","volume":"11","author":"Rossi","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41581-020-0297-2","article-title":"Plant-based diets to manage the risks and complications of chronic kidney disease","volume":"16","author":"Carrero","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_102","first-page":"598","article-title":"Dietary fiber intake is associated with chronic kidney disease (CKD) progression and cardiovascular risk, but not protein nutritional status, in adults with CKD","volume":"26","author":"Lu","year":"2017","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.2215\/CJN.02260314","article-title":"Dietary fiber, kidney function, inflammation, and mortality risk","volume":"9","author":"Xu","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2215\/CJN.0000000682","article-title":"High-Diversity Plant-Based Diet and Gut Microbiome, Plasma Metabolome, and Symptoms in Adults with CKD","volume":"20","author":"Stanford","year":"2025","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wathanavasin, W., Cheungpasitporn, W., Thongprayoon, C., and F\u00fcl\u00f6p, T. (2025). Effects of Dietary Fiber Supplementation on Modulating Uremic Toxins and Inflammation in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Toxins, 17.","DOI":"10.3390\/toxins17020057"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Jiang, H., Wang, X., Zhou, W., Huang, Z., and Zhang, W. (2025). Gut microbiota-derived short-chain fatty acids mediate the antifibrotic effects of traditional Chinese medicine in diabetic nephropathy. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1643515"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1080\/13880209.2024.2351946","article-title":"Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota","volume":"62","author":"Wu","year":"2024","journal-title":"Pharm. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e23-00024","DOI":"10.1097\/IMNA-D-23-00024","article-title":"Gut Microbiota-derived Metabolites: A New Perspective of Traditional Chinese Medicine Against Diabetic Kidney Disease","volume":"11","author":"Zhao","year":"2024","journal-title":"Integr. Med. Nephrol. Androl."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Yu, Z., Zhao, J., Qin, Y., Wang, Y., Zhang, Y., and Sun, S. (2022). Probiotics, Prebiotics, and Synbiotics Improve Uremic, Inflammatory, and Gastrointestinal Symptoms in End-Stage Renal Disease with Dialysis: A Network Meta-Analysis of Randomized Controlled Trials. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.984187"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Han, C. (2018). Update on FXR Biology: Promising Therapeutic Target?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072069"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1681\/ASN.2017020222","article-title":"FXR\/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity","volume":"29","author":"Wang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1681\/ASN.2014010042","article-title":"Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD","volume":"26","author":"Schulman","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_113","first-page":"12.20.24319427","article-title":"Role of Probiotics on Dialysis Patients in End-Stage Kidney Disease: A Systematic Review","volume":"2024","author":"Ahmed","year":"2024","journal-title":"medRxiv"},{"key":"ref_114","first-page":"Cd013631","article-title":"Synbiotics, prebiotics and probiotics for people with chronic kidney disease","volume":"10","author":"Cooper","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhang, M., Wang, X., Liu, P., Wang, L., Li, Y., Wang, X., and Ren, F. (2022). Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1037257"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Arteaga-Muller, G.Y., Flores-Trevi\u00f1o, S., Bocanegra-Ibarias, P., Robles-Espino, D., Garza-Gonz\u00e1lez, E., Fabela-Valdez, G.C., and Camacho-Ortiz, A. (2024). Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation. Nutrients, 16.","DOI":"10.3390\/nu16081109"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Cedillo-Flores, R., Cuevas-Budhart, M., Cavero-Redondo, I., Kappes, M., \u00c1vila-D\u00edaz, M., and Paniagua, R. (2025). Impact of Gut Microbiome Modulation on Uremic Toxin Reduction in Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis. Nutrients, 17.","DOI":"10.1101\/2025.02.21.25322662"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Bian, J., Liebert, A., Bicknell, B., Chen, X., Huang, C., and Pollock, C. (2022). Faecal Microbiota Transplantation and Chronic Kidney Disease. Nutrients, 14.","DOI":"10.3390\/nu14122528"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zhang, J., Ren, X., Li, B., Zhao, Z., Li, S., and Zhai, W. (2025). Fecal microbiota transplantation is a promising therapy for kidney diseases. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1628722"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Liu, C., Yang, L.-T., Wei, W., and Fu, P. (2024). Efficacy of probiotics\/synbiotics supplementation in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1434613"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T.U., Kim, H., and Kim, W. (2021). Effects of Probiotics, Prebiotics, and Synbiotics on Uremic Toxins, Inflammation, and Oxidative Stress in Hemodialysis Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194456"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/10408398.2020.1740645","article-title":"Probiotics, prebiotics, and synbiotics for the improvement of metabolic profiles in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials","volume":"61","author":"Zheng","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1053\/j.jrn.2022.04.001","article-title":"Probiotics, Prebiotics, and Synbiotics for Patients on Dialysis: A Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"33","author":"Chen","year":"2022","journal-title":"J. Ren. Nutr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1136\/gutjnl-2024-334634","article-title":"Toxic microbiome and progression of chronic kidney disease: Insights from a longitudinal CKD-Microbiome Study","volume":"74","author":"Laiola","year":"2025","journal-title":"Gut"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Liebman, S., and Joshi, S. (2022). Plant-Based Diets and Peritoneal Dialysis: A Review. Nutrients, 14.","DOI":"10.3390\/nu14061304"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Karimi, M., Shirsalimi, N., Hashempour, Z., Omran, H.S., Sedighi, E., Beigi, F., and Mortezazadeh, M. (2024). Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: A comprehensive literature review. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1439176"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e0006022","DOI":"10.1128\/cmr.00060-22","article-title":"Fecal microbiota transplantation: Current challenges and future landscapes","volume":"37","author":"Yadegar","year":"2024","journal-title":"Clin. Microbiol. Rev."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5648\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:21:24Z","timestamp":1784694084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,18]]},"references-count":127,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145648"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145648","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,18]]}}}